Safety and immunogenicity of Nanocovax, a SARS-CoV-2 recombinant spike protein vaccine: Interim results of a double-blind, randomised controlled phase 1 and 2 trial.

Background: Nanocovax is a recombinant severe acute respiratory syndrome coronavirus 2 subunit vaccine composed of full-length prefusion stabilized recombinant SARS-CoV-2 spike glycoproteins (S-2P) and aluminium hydroxide adjuvant. Methods: We conducted a dose-escalation, open label trial (phase 1) and a randomized, double-blind, placebo-controlled trial (phase 2) to evaluate the safety and immunogenicity of the Nanocovax vaccine (in 25 mcg, 50 mcg, and 75 mcg doses, aluminium hydroxide adjuvanted (0·5 mg/dose) in 2-dose regime, 28 days apart (ClinicalTrials.gov number, NCT04683484). In phase 1, 60 participants received two intramuscular injection of the vaccine following dose-escalation procedure. The primary outcomes were reactogenicity and laboratory tests to evaluate the vaccine safety. In phase 2, 560 healthy adults received either vaccine doses similar in phase 1 (25 or 50 or 75 mcg S antigen in 0·5 mg aluminium per dose) or adjuvant (0·5 mg aluminium) in a ratio of 2:2:2:1. One primary outcome was the vaccine safety, including solicited adverse events for 7 day and unsolicited adverse events for 28 days after each injection as well as serious adverse event or adverse events of special interest throughout the study period. Another primary outcome was anti-S IgG antibody response (Index unit/ml). Secondary outcomes were surrogate virus neutralisation (inhibition percentage), wild-type SARS-CoV-2 neutralisation (dilution fold), and T-cell responses by intracellular staining for interferon gamma (IFNg). Anti-S IgG and neutralising antibody levels were compared with convalescent serum samples from symptomatic Covid-19 patients. Findings: For phase 1 study, no serious adverse events were observed for all 60 participants. Most adverse events were grade 1 and disappeared shortly after injection. For phase 2 study, after randomisation, 480 participants were assigned to receive the vaccine with adjuvant, and 80 participants were assigned to receive the placebo (adjuvant only). Reactogenicity was absent or mild in the majority of participants and of short duration (mean ≤3 days). Unsolicited adverse events were mild in most participants. There were no serious adverse events related to Nanocovax. Regarding the immunogenicity, Nanocovax induced robust anti-S antibody responses. In general, there humoral responses were similar among vaccine groups which reached their peaks at day 42 and declined afterward. At day 42, IgG levels of vaccine groups were 60·48 [CI95%: 51·12-71·55], 49·11 [41·26-58·46], 57·18 [48·4-67·5] compared to 7·10 [6·32-13·92] of convalescent samples. IgG levels reported here can be converted to WHO international standard binding antibody unit (BAU/ml) by multiplying them to a conversion factor of 21·8. Neutralising antibody titre of vaccine groups at day 42 were 89·2 [52·2-152·3], 80·0 [50·8-125.9] and 95·1 [63·1-143·6], compared to 55·1 [33·4-91·0] of the convalescent group. Interpretation: Up to day 90, Nanocovax was found to be safe, well tolerated, and induced robust immune responses. Funding: This work was funded by the Coalition for Epidemic Preparedness Innovations (CEPI), the Ministry of Science and Technology of Vietnam, and Nanogen Pharmaceutical Biotechnology JSC.

Increases in both HIV and syphilis among men who have sex with men in Vietnam: Urgent need for comprehensive responses.

The objective of this study was to determine the temporal trends and factors associated with HIV and syphilis infection among men who have sex with men (MSM) in southern Vietnam. Data from the 2014-2018 national HIV sentinel surveillance of MSM aged 16 years or older were collected from three provinces, including An Giang (N = 761), Can Tho (N = 900), and Ho Chi Minh City (N = 1426), and examined for changes in prevalence rates of HIV and syphilis and risk behaviors over time. Multivariate logistic regression was performed to assess the trends and correlates of HIV and syphilis infections among MSM. There were upward trends for HIV (9.5% in 2014 to 14.2% in 2018, p-trend<0.01), syphilis (4.9% in 2014 to 8.0% 2018, p-trend<0.01), and HIV/syphilis co-infection (1.9% in 2014 to 3.1% in 2018, p-trend=0.01). Factors associated with HIV infection included place of residence, early sexual debut, consistent condom use and not engaging in anal sex during the past month, not knowing one's HIV test results, having ever injected drugs, and having active syphilis. Additionally, early sexual debut and being HIV positive were associated with syphilis infection. Rising prevalences of these infections among MSM suggests an urgent need for comprehensive intervention packages for HIV/STI prevention.

Genome-wide analysis of SARS-CoV-2 strains circulating in Vietnam: Understanding the nature of the epidemic and role of the D614G mutation.

Genome-wide analysis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strains is essential to better understand infectivity and virulence and to track coronavirus disease 2019 (COVID-19) cases and outbreaks. We performed whole-genome sequencing of 27 SARS-CoV-2 strains isolated between January 2020 and April 2020. A total of 54 mutations in different genomic regions was found. The D614G mutation, first detected in March 2020, was identified in 18 strains and was more likely associated with a lower cycle threshold (<25) in real-time reverse-transcription polymerase chain reaction diagnostic tests than the original D614 (prevalence ratio = 2.75; 95% confidence interval, 1.19-6.38). The integration of sequencing and epidemiological data suggests that SARS-CoV-2 transmission in both quarantine areas and in the community in Vietnam occur at the beginning of the epidemic although the country implemented strict quarantine quite early, with strict contact tracing, and testing. These findings provide insights into the nature of the epidemic, as well as shape strategies for COVID-19 prevention and control in Vietnam.

Estimating and mitigating the risk of COVID-19 epidemic rebound associated with reopening of international borders in Vietnam: a modelling study.

BACKGROUND: Vietnam has emerged as one of the world's leading success stories in responding to COVID-19. After a prolonged period of little to no transmission, there was an outbreak of unknown source in July, 2020, in the Da Nang region, but the outbreak was quickly suppressed. We aimed to use epidemiological, behavioural, demographic, and policy data from the COVID-19 outbreak in Da Nang to calibrate an agent-based model of COVID-19 transmission for Vietnam, and to estimate the risk of future outbreaks associated with reopening of international borders in the country. METHODS: For this modelling study, we used comprehensive data from June 15 to Oct 15, 2020, on testing, COVID-19 cases, and quarantine breaches within an agent-based model of SARS-CoV-2 transmission to model a COVID-19 outbreak in Da Nang in July, 2020. We applied this model to quantify the risk of future outbreaks in Vietnam in the 3 months after the reopening of international borders, under different behavioural scenarios, policy responses (ie, closure of workplaces and schools), and ongoing testing. FINDINGS: We estimated that the outbreak in Da Nang between July and August, 2020, resulted in substantial community transmission, and that higher levels of symptomatic testing could have mitigated this transmission. We estimated that the outbreak peaked on Aug 2, 2020, with an estimated 1060 active infections (95% projection interval 890-1280). If the population of Vietnam remains highly compliant with mask-wearing policies, our projections indicate that the epidemic would remain under control even if a small but steady flow of imported infections escaped quarantine into the community. However, if complacency increases and testing rates are relatively low (10% of symptomatic individuals are tested), the epidemic could rebound again, resulting in an estimated 2100 infections (95% projected interval 1050-3610) in 3 months. These outcomes could be mitigated if the behaviour of the general population responds dynamically to increases in locally acquired cases that exceed specific thresholds, but only if testing of symptomatic individuals is also increased. INTERPRETATION: The successful response to COVID-19 in Vietnam could be improved even further with higher levels of symptomatic testing. If the previous approaches are used in response to new COVID-19 outbreaks, epidemic control is possible even in the presence of low levels of imported cases. FUNDING: Ministry of Science and Technology (Vietnam). TRANSLATION: For the Vietnamese translation of the abstract see Supplementary Materials section.

Determinants of Risk Factors for Renal Impairment among HIV-Infected Patients Treated with Tenofovir Disoproxil Fumarate-Based Antiretroviral Regimen in Southern Vietnam.

BACKGROUND: The situation of renal impairment among HIV-infected patients treated with TDF-based antiretroviral (ARV) regimen greater than 3 years is little known when TDF use has been promptly increasing in Vietnam. METHODS: We analyse demographic and clinical data from a cross-sectional survey of 400 HIV-infected patients aged ≥18 years, who were treatment-naive or switched TDF regimen within over 3 years between November 2018 and March 2019. Serological tests for serum creatinine, ALT, and AST were performed. Renal impairment was defined as an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2. Multivariate regression analyses were used to explore the risk factors associated with renal impairment. RESULTS: At the baseline, 7.8% of respondents had estimated glomerular filtration rate (eGFR) of 30-59 mL/min/1.73 m2 and 0.8% had eGFR of 15-29 mL/min/1.73 m2, out of 34 (8.5%) of participants who had renal impairment. Multivariate analysis showed that participants who had preexposure to isoniazid (adjusted PR [aPR] = 0.35 Cl: 0.14-0.91) compared with nonexposure to isoniazid who had a BMI from 18.5 up to 25 kg/m2 (aPR = 0.31 Cl: 0.15-0.62) compared with BMI below 18.5 kg/m2 were less likely to suffer from renal impairment. Patients aged greater than 60 years (aPR = 26.75, 95% Cl: 3.38-211.62) compared with those aged 20-29 years were more likely to have increased risk of renal impairment. CONCLUSION: Our findings underscore the need for longitudinal studies to assess the influence of TDF on maintaining the low prevalence of renal impairment among HIV-infected patients in Vietnam.

Clinical features, isolation, and complete genome sequence of severe acute respiratory syndrome coronavirus 2 from the first two patients in Vietnam.

In January 2020, we identified two severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected patients in a familial cluster with one person coming from Wuhan, China. The complete genome sequences of two SARS-CoV-2 strains isolated from these patients were identical and 99.98% similar to strains isolated in Wuhan. This is genetically suggestive of human-to-human transmission of SARS-CoV-2 and indicates Wuhan as the most plausible origin of the early outbreak in Vietnam. The younger patient had a mild upper respiratory illness and a brief viral shedding, whereas the elderly with multi-morbidity had pneumonia, prolonged viral shedding, and residual lung damage. The evidence of nonsynonymous substitutions in the ORF1ab region of the viral sequence warrants further studies.

Emergence of New Delhi Metallo-Beta-Lactamase (NDM) and Klebsiella pneumoniae Carbapenemase (KPC) Production by Escherichia coli and Klebsiella pneumoniae in Southern Vietnam and Appropriate Methods of Detection: A Cross-Sectional Study.

Carbapenemase-producing Enterobacteriaceae (CPE) are well known to cause many serious infections resulting in increasing mortality rate, treatment cost, and prolonged hospitalization. Among the widely recognized types of carbapenemases, New Delhi ß-lactamase (NDM) and Klebsiella pneumoniae carbapenemase (KPC) are the most important enzymes. However, in Vietnam, there are only scattered reports of CPE due to the lack of simple and affordable methods that are suitable to laboratory conditions. This study aims to survey the characteristics of carbapenem-resistant E. coli and K. pneumoniae (CR-E/K) at two hospitals in Southern Vietnam and perform some simple methods to detect the two enzymes. A total of 100 CR-E/K strains were collected from clinical isolates of Gia Dinh People's Hospital and Dong Nai General Hospital, Vietnam, from November 2017 to May 2018. The patient-related information was also included in the analysis. We conducted real-time polymerase chain reaction (PCR), Modified Hodge Test (MHT), and combined disk test (CDT) on all isolates. Carbapenemase-encoding genes were detected in 47 isolates (36 NDM, 10 KPC, and one isolate harboring both genes). The E. coli strain carrying simultaneously these two genes was the first case reported here. Most of isolates were collected from patients in ICU, Infectious Disease Department, and Department of Urologic Surgery. Urine and sputum were two common specimens. The true positive rate (sensitivity, TPR) and specificity (SPC) of the imipenem-EDTA (ethylen diamine tetra acetic acid) for NDM detection and the imipenem-PBA (phenylboronic acid) for KPC detection on E. coli were 93.8%, 97.1% and 66.7%, 95.7%, respectively. Meanwhile, the imipenem-EDTA for NDM detection and the imipenem-PBA for KPC detection among K. pneumonia achieved 90.5%, 100% and 100%, 92.9% TPR and SPC, respectively. However, MHT showed low sensitivity and specificity. Our findings showed that CP-E/K were detected with high prevalence in the two hospitals. We suggest that CDT can be used as a low-priced and accurate method of detection.

Fatal avian influenza A(H5N1) infection in a 36-week pregnant woman survived by her newborn in Sóc Trang Province, Vietnam, 2012.

BACKGROUND: Reports of pregnant women infected with avian influenza are rare. Studies showed that A/H5N1 virus can penetrate the placental barrier and infect the fetus. Of six documented cases, four died and two survivors had a spontaneous abortion. OBJECTIVES: We report a clinical, outcome and epidemiological characteristics of a 36-week pregnant woman infected with A/H5N1 and her newborn in Soc Trang province of Vietnam in 2012. METHODS: Epidemiological and laboratory investigations were conducted. Clinical manifestations, progress, treatment and outcome of the case-patient and her newborn were collected. Human tracheal aspirate, throat swab and serum specimens were tested for influenza A/H5N1, A/H3N1, A/H1N1pdm09 and B by real-time RT-PCR and genome sequencing. Poultry throat and rectal swabs were tested by PCR and virus isolation. RESULTS: Case-patient hospitalized with high fever and cough, and died after onset 6 days. She continuously slaughtered sick poultry 5 days before illness onset. Clinical manifestation showed rapid progressive severe pneumonia. Her tracheal aspirate sample was positive influenza A/H5N1 virus. Her new-born was delivered by caesarean section with low birth weight and early onset pneumonia, however fully recovered after 16 days treatment. Neonate's throat swabs and paired serum samples tested negative for influenza A/H5N1. Clade 1.1 A/H5N1 virus was detected in poultry samples, was same clade and highly homogenous with the virus was detected in the mother. CONCLUSIONS: This was the first documented a live birth from a pregnant woman infected with influenza A/H5N1 virus. Intensive studies are needed to better understand mother-to-child transmission of influenza A/H5N1 virus.

Zika preparedness and response in Viet Nam.

The findings and conclusions in this article are those of the authors and do not necessarily represent the official positions of the United States Centers for Disease Control and Prevention.

Cholera returns to southern Vietnam in an outbreak associated with consuming unsafe water through iced tea: A matched case-control study.

BACKGROUND: After more than a decade of steadily declining notifications, the number of reported cholera cases has recently increased in Vietnam. We conducted a matched case-control study to investigate transmission of cholera during an outbreak in Ben Tre, southern Vietnam, and to explore the associated risk factors. METHODOLOGY/PRINCIPAL FINDINGS: Sixty of 71 diarrheal patients confirmed to be infected with cholera by culture and diagnosed between May 9 and August 3, 2010 in Ben Tre were consecutively recruited as case-patients. Case-patients were matched 1:4 to controls by commune, sex, and 5-year age group. Risk factors for cholera were examined by multivariable conditional logistic regression. In addition, environmental samples from villages containing case-patients were taken to identify contamination of food and water sources. The regression indicated that drinking iced tea (adjusted odds ratio (aOR) = 8.40, 95% confidence interval (CI): 1.84-39.25), not always boiling drinking water (aOR = 2.62, 95% CI: 1.03-6.67), having the main source of water for use being close to a toilet (aOR = 4.36, 95% CI: 1.37-13.88), living with people who had acute diarrhea (aOR = 13.72, 95% CI: 2.77-67.97), and little or no education (aOR = 4.89, 95% CI: 1.18-20.19) were significantly associated with increased risk of cholera. In contrast, drinking stored rainwater (aOR = 0.17, 95% CI: 0.04-0.63), eating cooked seafood (aOR = 0.27, 95% CI: 0.10-0.73), and eating steamed vegetables (aOR = 0.22, 95% CI: 0.07-0.70) were protective against cholera. Vibrio cholerae O1 Ogawa carrying ctxA was found in two of twenty-five river water samples and one of six wastewater samples. CONCLUSIONS/SIGNIFICANCE: The magnitude of the cholera outbreak in Ben Tre was lower than in other similar settings. This investigation identified several risk factors and underscored the importance of continued responses targeting cholera prevention in southern Vietnam. The association between drinking iced tea and cholera and the spread of V. cholerae O1, altered El Tor strains warrant further research. These findings might be affected by a number of limitations due to the inability to capture asymptomatic or mildly symptomatic infections, the possible underreporting of personal unhygienic behaviors, and the purposive selection of environmental samples.

Clinical characteristics of hand, foot and mouth disease in Daklak Province, Vietnam and associated factors of severe cases.

The Hand, Foot and Mouth Disease (HFMD) outbreaks occurred throughout Daklak province, Vietnam in 2011. This study reviewed all 744 medical records of HFMD patients admitted to Daklak Hospital in 2011 to describe the clinical characteristics of HFMD patients and determined factors associated with severe illness. Among 744 patients, 63 (8.5%) cases were severe. Most (695, 93.4%) of the cases were 3 years old or younger, and 464 (62.4%) were boys. The number of cases peaked between August and November. Most (726, 97.6%) recovered, 17 severe cases (2.3%) were transferred to higher level hospitals, and one death. Symptoms at admission included fever (93.5% had a fever ≥ 38.5 °C), blisters (99.1%), myoclonus (58.5%), and leukocytosis (> 11,300/mm3: 38.8%). Viral cultures were performed for 61 of 63 severe cases, of which 26.2% were positive for Enteroviruses. Multivariable analysis found that oral ulcers (Odds Ratio (OR) 3.74; 95% Confidence Interval (CI) 2.13-6.58), myoclonus (OR 44.75; 95% CI 6.04-331.66) and high white blood cell count (OR 1.08; 95% CI 1.01-1.16 per 1000/mm3 increase) were significantly associated with severe illness. HFMD mainly occurs in children younger than 3 years old and rainy season. Oral ulcers, myoclonus, and leukocytosis should be closely monitored to promptly detect severe cases of HFMD.

Epidemiological and clinical characteristics of children who died from hand, foot and mouth disease in Vietnam, 2011.

BACKGROUND: In 2011, a large outbreak of hand, foot and mouth disease (HFMD) in Vietnam resulted in 113,121 children seeking medical attention, of whom170 died. Understanding the epidemiology of fatal HFMD may improve treatment and help targeting prevention activities for vulnerable populations. We describe epidemiological and clinical characteristics of children who died from HFMD in Vietnam in 2011. METHODS: Clinical data were obtained through reviewing medical records of the deaths occurring from January through December 2011 in all hospitals in Vietnam. Hospitals reported any deaths among patients with laboratory-confirmed enterovirus (EV) infection to the Ministry of Health. Data were extracted from the national database. RESULTS: Of the 169 deaths reviewed for whom records were available, 87% were 3-year-old or younger, 69% were male, 18% attended daycare, 89% lived in Southern Vietnam, and 85% of the deaths occurred between May-October 2011. One hundred thirty (77%) cases sought treatment in a hospital within three days of onset of illness. Symptoms at admission included fever (98%), myoclonus (66%), vomiting (53%), oral ulcers (50%) and vesicular erythema (50%). One hundred six (75%) cases had leukocytosis and 91 (54%) had hyperglycemia. One hundred three (61%) tested positive for EV, of which 84 (82%) were positive for EV71. CONCLUSIONS: Deaths associated with HFMD occurred throughout 2011 among males three years or younger who were cared for at home. The HFMD control program should focus on interventions at the household level. Clinicians should be alerted to symptoms suggestive of severe HFMD including fever, myoclonus, vomiting, oral ulcers and vesicles with high white blood cell count especially in young children.